{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T23:00:46Z","timestamp":1790550046747,"version":"4.1.0"},"reference-count":0,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2007,9,4]],"date-time":"2007-09-04T00:00:00Z","timestamp":1188864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2007,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Cobalamin is an essential cofactor for two mammalian enzymes: methionine synthase and methylmalonyl\u2010CoA mutase. Patients with the cobalamin C (CblC) defect have combined methylmalonic aciduria and homocystinuria. Recently, the gene responsible for the CblC type, <jats:italic>MMACHC<\/jats:italic>, was identified, which enables molecular diagnostics. In this study, we describe two siblings, a 16\u2010year\u2010old girl and her 11\u2010year\u2010old brother, of a consanguineous family who presented with a very distinct clinical manifestation. The girl presented at the age of 13 years with macrocytic anaemia, cognitive regression and Marfanoid features such as increased arm\u2010span, arachnodactyly, joint hyperlaxity and scoliosis. Her brother presented at the age of 10 months with developmental delay and behavioural abnormalities. Biochemical analysis showed severely increased homocysteine and methylmalonic acid levels in plasma of both siblings. In addition, plasma cysteine levels were decreased in the girl but not in her brother. The diagnosis of CblC defect was confirmed by genomic sequencing of the coding exons of the <jats:italic>MMACHC<\/jats:italic> gene. Two heterozygous mutations were identified in both siblings; the common c.271dupA p.Arg91LysfsX14 and a novel mutation, c.1A&gt;G p.Met1?. Therapy consisting of folic acid, vitamin B<jats:sub>6<\/jats:sub>, l\u2010carnitine and intramuscular vitamin B<jats:sub>12<\/jats:sub> resulted in a clear improvement of biochemical parameters and, importantly, resulted in amelioration of the Marfanoid features in the girl. These data might suggest that low cysteine levels account for the Marfanoid features observed in the girl and indicate that the CblC type of combined methylmalonic aciduria and homocystinuria should be considered in the differential diagnosis of patients with Marfanoid features.<\/jats:p>","DOI":"10.1007\/s10545-007-0546-6","type":"journal-article","created":{"date-parts":[[2007,9,3]],"date-time":"2007-09-03T03:06:16Z","timestamp":1188788776000},"page":"811-811","source":"Crossref","is-referenced-by-count":22,"title":["Marfanoid features in a child with combined methylmalonic aciduria and homocystinuria (CblC type)"],"prefix":"10.1002","volume":"30","author":[{"given":"Sandra G.","family":"Heil","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Laboratory of Pediatrics and Neurology Radboud University Nijmegen Medical Centre P.O. Box 9101 Nijmegen 6500 HB The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marije","family":"Hogeveen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Laboratory of Pediatrics and Neurology Radboud University Nijmegen Medical Centre P.O. Box 9101 Nijmegen 6500 HB The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo A. J.","family":"Kluijtmans","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Laboratory of Pediatrics and Neurology Radboud University Nijmegen Medical Centre P.O. Box 9101 Nijmegen 6500 HB The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. J.","family":"van Dijken","sequence":"additional","affiliation":[{"name":"St Elisabeth Hospital Tilburg The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard B.","family":"van de Berg","sequence":"additional","affiliation":[{"name":"St Elisabeth Hospital Tilburg The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk J.","family":"Blom","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Laboratory of Pediatrics and Neurology Radboud University Nijmegen Medical Centre P.O. Box 9101 Nijmegen 6500 HB The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Morava","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Laboratory of Pediatrics and Neurology Radboud University Nijmegen Medical Centre P.O. Box 9101 Nijmegen 6500 HB The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,9,4]]},"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-007-0546-6","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T05:02:11Z","timestamp":1694754131000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-007-0546-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,9,4]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2007,10]]}},"alternative-id":["10.1007\/s10545-007-0546-6"],"URL":"https:\/\/doi.org\/10.1007\/s10545-007-0546-6","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,9,4]]}}}